The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase.
The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13,16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase.
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DOI：
10.1016/s0021-9258(18)54882-1
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发表时间：
1991-10
期刊：
影响因子：
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通讯作者：
A. Voss;M. Reinhart;S. Sankarappa;H. Sprecher
中科院分区：
文献类型：
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作者：
A. Voss;M. Reinhart;S. Sankarappa;H. Sprecher
从亚麻酸生物合成4，7，10，13，16，19 -22：6的最后一步是由酰基-CoA-依赖性4-去饱和酶催化的假设从未通过直接实验进行评估。当大鼠肝微粒体与[1- 14 C] 7，10，13，16，19 -22：5在亚油酸容易去饱和至6，9，12 -18：3的条件下孵育时，不可能检测到推定的4-去饱和酶的产物。在丙二酰-CoA的存在下，将7、10、13、16、19 -22：5依次链延长至9、12、15、18、21 -24：5，然后在6位去饱和，得到6、9、12、15、18、21 -24：6。微粒体以9、12、15、18、21 -24：5的速率去饱和，与亚油酸代谢至6、9、12 -18：3的速率相似。大鼠肝细胞代谢[1- 14 C] 7、10、13、16、19 -22：5至22：6（n-3），但此外，还可能在磷脂中检测到少量酯化的24：5（n-3）和24：6（n-3），这一发现与其作为22：6（n-3）生物合成中的必然中间体的作用一致。当3- 14 C标记的24：5（n-3）或24：6（n-3）与肝细胞孵育时，仅少量的任一底物被酯化。[3- 14 C] 24：5（n-3）通过β-氧化为22：5（n-3）和作为24：6（n-3）和22：6（n-3）生物合成的前体代谢。[3- 14 C]24：6（n-3）的主要代谢归宿是β-氧化为22：6（n-3），然后酰化为膜脂质。因此，我们的研究结果证明，22：5（n-3）是22：6（n-3）的前体，但通过一个独立的4-去饱和酶的途径。该途径涉及微粒体链从22：5（n-3）延长至24：5（n-3），然后去饱和至24：6（n-3）。然后，该微粒体产物通过β-氧化代谢为22：6（n-3）。
The hypothesis that the last step in the biosynthesis of 4,7,10,13,16,19-22:6 from linolenate is catalyzed by an acyl-CoA-dependent 4-desaturase has never been evaluated by direct experimentation. When rat liver microsomes were incubated with [1-14C]7,10,13,16,19-22:5, under conditions where linoleate was readily desaturated to 6,9,12-18:3, it was never possible to detect the product of the putative 4-desaturase. In the presence of malonyl-CoA, 7,10,13,16,19-22:5 was sequentially chain-elongated to 9,12,15,18,21-24:5, followed by its desaturation at position 6 to give 6,9,12,15,18,21-24:6. Microsomes desaturated 9,12,15,18,21-24:5 at rates similar to those observed for metabolizing linoleate to 6,9,12-18:3. Rat hepatocytes metabolize [1-14C]7,10,13,16,19-22:5 to 22:6(n-3), but in addition, it was possible to detect small amounts of esterified 24:5(n-3) and 24:6(n-3) in phospholipids, which is a finding consistent with their role as obligatory intermediates in 22:6(n-3) biosynthesis. When 3-14C-labeled 24:5(n-3) or 24:6(n-3) were incubated with hepatocytes, only a small amount of either substrate was esterified. [3-14C] 24:5(n-3) was metabolized both by beta-oxidation to 22:5(n-3) and by serving as a precursor for the biosynthesis of 24:6(n-3) and 22:6(n-3). The primary metabolic fate of [3-14C]24:6(n-3) was beta-oxidation to 22:6(n-3), followed by its acylation into membrane lipids. Our results thus document that 22:5(n-3) is the precursor for 22:6(n-3) but via a pathway that is independent of a 4-desaturase. This pathway involves the microsomal chain elongation of 22:5(n-3) to 24:5(n-3), followed by its desaturation to 24:6(n-3). This microsomal product is then metabolized, via beta-oxidation, to 22:6(n-3).